The mechanism and control of the oxidative metabolism of drugs, steroids, and carcinogenic agents, alcohols, and other xenobiotics by cytochrome P-450 will be further explored. The kinetics of formation and the chemistry of key intermediates during oxygen activation will be evaluated by rapid and sensitive spectrophotometric techniques as well as other physical biochemical methods. Drug metabolites will be identified by chromatography and mass spectrometry. Changes in the pattern of drug metabolism resulting from drug or other chemical treatment of animals, protein malnutrition, steroid hormone and inhibitor treatment will be evaluated. Particular emphasis will be directed to a study of cytochrome P-450 function in steroidogenic organs to determine changes in hormones during drug treatment. Extension of the methodology to human tissues will be continued to compare the properties and possible genetic variation in drug metabolism. Use of cellular and subcellular systems will be employed to monitor the relationship of drug and steroid metabolism to glycolysis, fatty acid biosynthesis and other metabolic reactions within the cell.